A Clinical Trial to evaluate AL002 in Participants with early Alzheimer's Disease
- Conditions
- Early Alzheimer’s DiseaseMedDRA version: 20.0Level: SOCClassification code 10029205Term: Nervous system disordersSystem Organ Class: 10029205 - Nervous system disordersTherapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2019-001476-11-PL
- Lead Sponsor
- Alector Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 265
1.Participant must be in the AD continuum as defined by the 2018 NIA-AA Research Framework; this requires evidence of cerebral amyloidosis (A+) as detailed:a.Must be positive by the PrecivityADAß blood test prior to proceeding with either the amyloid-PET or CSF studies for confirmation of amyloid beta (Aß) pathology. Demonstration of amyloid pathology by amyloid-PET or CSF phosphorylated tau (pTau)/ amyloid beta (1-42) (Aß42) ratio is required. Participants with a positive historical amyloid-PET scan that has been collected =24 months prior to the start of screening and meets the acceptable criteria for a historical amyloid-PET scan as outlined in Inclusion Criteria 1b will not be tested by P PrecivityADAß . Participants with a validated positive historical amyloid-PET scans are considered positive for cerebral Aß pathology without further testing, with an intermediate APS may proceed to confirmation, and with low APS are not eligible. b.Has evidence of the AD amyloid pathology, as demonstrated either by positive amyloid-PET scan or by a CSF pTau/Aß42 ratio > 0.024 as measured by the Elecsys assay. Historical amyloid-PET may be allowed to fulfil this criterion; historical CSF measurements will not be allowed to fulfil this criterion.2.Participants must demonstrate a clinical severity consistent with Stages 2, 3 or early 4 as defined in the 2018 NIA-AA Research Framework, also described as mild cognitive impairment and mild dementia. Further, participants must meet the following inclusion criteria to define clinical severity: a.Has mild symptomatology as defined by a screening MMSE score of =22 points. b.Has a Clinical Dementia Rating – Global Score of 0.5 to 1.0. c.Has evidence of episodic memory impairment as defined by a RBANS score on the Delayed Memory Index =85.3.If Participant is receiving symptomatic AD medications, the dosing regimen must have been stable for 90 days prior to screening not expected to change during study, and must not be initiated, modified, or stopped within 90 days prior to screening start.4.Participant is willing and able to give informed consent. Where not permitted by local regulations, participants deemed not able to provide consent by the PI will not be enrolled, where local regulation permit it, a legally authorized representative must provide informed consent on their behalf, and participant must provide assent.5.Participant can be male or female, and is 50 to 85 age inclusive.6.Participant weighs between 45 to 120 kg, inclusive.7. At screening, female participants must be nonpregnant and nonlactating, and 1 of the following conditions must apply: a.Participant is not a WOCBP (either surgically sterilized, or physiologically incapable of becoming pregnant, or at least 1y postmenopausal.b.Participant is a WOCBP and agrees to use an acceptable contraceptive method from screening until12 weeks after the last dose of study treatment. Acceptable contraception is defined on the protocol. c.WOCBP must have a serum pregnancy test conducted at screening.8.Male participants must agree to use acceptable contraception and not donate sperm from screening until 12 weeks after the last dose of study. Acceptable contraception for the male participant when having sexual intercourse with a WOCBP who is not currently pregnant is defined as using a condom. In addition, WOCBP partners must use hormonal contraceptives or an intrauterine device. Vasectomized male participants should have received medical assessment of surg
1.Participant has any evidence of a condition other than AD that may affect cognition2.Participant has history or presence of vascular disease that has the potential to affect cognitive function, or stroke within past 2y, ischemic attack within last 180d before screening, or presence on MRI of any cortical stroke regardless of age.3.Participant has history of severe, clinically significant CNS trauma, history or presence of intracranial tumor, infections that affect brain function, or history of infections with neurologic sequelae4. Participant currently has or has had an acute illness that requires or required IV antibiotics within 30d prior to first study treatment admin.5Participant has history or presence of systemic autoimmune disorders that potentially cause progressive neurologic disease with associated cognitive deficits, or any ongoing eye disorder as per protocol 6.Participant has any history of schizophrenia, schizoaffective disorder, major depression, bipolar disorder, or is at risk of suicide in PI´s opinion7.Participant has history of alcohol and/or moderate to severe substance use disorder within the past 2y 8.Participant has MRI evidence of a. >2 lacunar infarcts. b. Any territorial infarct >1 cm3. c. White matter hyperintense lesions on the FLAIR sequence as per protocol 9.Participant has presence on MRI of microbleeds>5 and/or areas of leptomeningeal hemosiderosis as per protocol10.Participant has presence of significant cerebral vascular pathology, as assessed by the MRI central reader11.Participant is unable to tolerate MRI procedures or has a contraindication12.Participant has uncontrolled hypertension at screening or has a history or presence of an abnormal ECG13.Participant has history or presence of ventricular dysrhythmias or risk factors for them clinically significant14.Participant has significant kidney disease as per protocol15.Participant has impaired hepatic function as per protocol16.Participant is positive for hepatitis B surface Ag, total hepatitis B core antibody, HIV-1 or -2 antibodies or antigen, or history of spirochetal infection of the CNS. Participants with a positive hepatitis C virus antibody will be allowed if hepatitis C RNA is negative17.Participants with active or latent TB disease should not be enrolled 18. Any chronic active immune disorder requiring systemic immunosuppressive therapy within 1y prior to study enrollment19.Participant has abnormal screening TSH20.Participant has screening folic acid or low vitamin B12 levels that may be contributing to cognitive impairment21.Participant has screening hemoglobin A1c >8% or poorly controlled diabetes22.Participant has contraindication for LP including deformity of the lumbosacral region of the spine that in the PI´s opinion would contraindicate LP for participants in Part 1 and Part 2 who can only be CSF eligible due to regional lack of availability of PET ligands, or consent to the optional LP assessments 23.Participant has clinically significantly abnormal screening blood or urine results that remain abnormal, or has impaired coagulation24.Participant has history of cancer with the exceptions descrived in the protocol: 25.Participant has known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins 26.Participant has had any surgery or hospitalization within 30d prior to first study treatment admin 27.Participant with other severe or unstable medi
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method